Dissertations and Theses

Date of Degree

1-1-2020

Document Type

Dissertation

Degree Name

Doctor of Philosophy (Ph.D.)

Department

Epidemiology and Biostatistics

Advisor(s)

Denis Nash

Committee Members

Charles Cleland

Bruce Schackman

Katarzyna Wyka

Subject Categories

Public Health

Keywords

hepatitis c virus, people who use drugs, hcv care continuum, community viral load, hcv incidence and prevalence, opioid agonist therapy

Abstract

Abstract

Introduction

The incidence of Hepatitis C virus (HCV) infection has increased in the current opioid epidemic in the United States; current estimates are that 2-3 million Americans have HCV infection. The ongoing and increasing HCV epidemic among people who use drugs (PWUD) is occurring in the context of known HCV prevention and highly efficacious and well-tolerated curative HCV treatment. The development of direct acting antivirals (DAAs) with cure rates approaching 100% dramatically changed the treatment landscape. This provides both the potential for improved individual- and population-level treatment effectiveness, and also the potential for population-level HCV ‘cure as prevention' (CasP) (a key component of combined prevention) and consideration of the goal of HCV elimination. Medication assisted treatment (MAT) for opioid use disorder (OUDs) is another important component of combined HCV prevention. However, the impact of specific MAT program factors on HCV incidence remain underexplored.

Assessments of the HCV care continuum have identified large gaps in the sequential steps of HCV prevention and care. Community viral load (CVL) is a measure that has been developed to aide HIV surveillance and control but has not been developed for HCV surveillance despite many commonalities between HIV and HCV with respect to transmission, prevention and treatment. Hence, novel measures of HCV CVL merit study as predictors to identify vulnerable areas and populations, and as predictors of incidence, to help focus implementation of prevention and treatment and resources.

This dissertation examines outcomes of the HCV care continuum, and factors associated with linkage to HCV treatment, among PWUD in MAT, proposes novel HCV CVL measures, and examines HCV incidence, and individual-level factors associated with incidence, and the association of HCV CVL with area-level HCV incidence in an open cohort of patients receiving MAT.

Methods

Paper 1: A systematic review was conducted to identify conceptual and empirical applications of CVL constructs to HCV epidemiology. Using the published literature on HCV epidemiology and the HIV CVL literature, this Paper conceptualized and defined a set of HCV CVL measures constructed to address specific questions for defined populations.

Papers 2 and 3: This is an observational retrospective study of an open cohort of people receiving MAT in the form of methadone for OUDs at the Mount Sinai Health System (MSHS) opioid treatment program (OTP) in New York City (NYC), the largest not-for-profit OTP in the US. The study period is 2013-2016.

Paper 2: Data from patients were used to: 1) identify HCV care continuum outcomes (antibody and viral load (VL) testing; linkage-to-care; treatment receipt; and cure), 2) operationalize, calculate and examine geographic variation in engaged-in-care HCV CVLs, 3) calculate both documented and estimated unmet testing and treatment need, and 4) examine factors associated with linkage-to-HCV-care in the current era of DAAs and after implementation of qualitative reflex VL testing.

Paper 3: HCV incidence was calculated among those HCV antibody tested >2 times. HCV CVL was calculated among those with documented, active infection overall and by geographic area of residence. Incidence rates, incidence rate ratios, and associated factors overall and among specific subgroups were examined. Kaplan-Meier and Cox proportional hazard models were used to assess time-to-HCV-seroconversion.

Results

Paper 1: The systematic review found that there were no published studies either conceptualizing or applying CVL measures to HCV identifying this as an important gap in the literature. Five novel HCV CVL measures were conceptualized, using the literature on HCV epidemiology and the literature applying CVL to HIV epidemiology. This paper makes a novel and substantive contribution to the literature by developing CVL measures applicable to HCV epidemiology. This set of HCV CVL measures could be utilized to address diverse questions relevant to HCV control. One HCV CVL measure (‘engaged-in-care’) was identified to be calculated and examined further in Papers 2 and 3.

Paper 2: The study included 11,267 patients. Proportions of those HCV antibody tested (52.5% -vs. 73.3%), linked to HCV care (15.7% vs 51.8%), and receiving HCV treatment (12.0% vs 44.7%) all increased significantly in 2015-16 compared with 2013-14 after implementation of on-site qualitative reflex VL testing. Hispanic ethnicity was associated with lower linkage to HCV care and Manhattan residence was associated with better linkage to care. The engaged-in-care HCV CVL measure was 6.06 log10 copies/milliliter (standard deviation: 0.926) and varied significantly by demographic subgroups and geography. Documented unmet treatment need among those engaged in care decreased significantly (88.0% vs. 55.0%) but remained high; estimated unmet treatment need among the entire study population was higher still (99.1% vs 86.0%).

Paper 3: Among 8,352 patients tested, HCV prevalence was 48.7%. Among 2,535 patients seronegative at first antibody test, HCV incidence was 2.25/100 person-years of observation (PYO). Incidence was 6.70/100 PYO among those reporting main drug use by injection. Female gender, drug injection, and lower MAT retention were significantly associated with higher incidence. Female gender, drug injection and methadone doses log10 increase in HCV CVL, the HCV incidence rate was expected to be multiplied by about 2.7; although this association was not statistically significant, these results suggest the importance of further research on this association.

Discussion

This dissertation demonstrates that HCV CVL measures can be constructed and that there are significant area-level disparities in HCV CVL. My data suggest that measures of HCV CVL may be valuable in geographically focusing prevention and treatment efforts and that HCV CVL measures merit further study as potential predictors of HCV incidence.

Analyses identified significant gaps in the HCV care continuum steps of testing, linkage-to-care, and treatment. Further improvements in rates of complete testing are needed and broader implementation of HCV reflex testing may be valuable. More effective linkage to care interventions are needed generally and particularly for those of Hispanic ethnicity. While during the study period the proportion HCV treated increased significantly, there were still very high rates of unmet treatment need suggesting that HCV control will require significant expansion of HCV treatment.

The incidence rates observed support recommendations for annual HCV testing of all those in MAT, not only those who report injecting drugs. Data highlight the need for efforts to improve MAT retention and ensure adequate dosing. Further studies of and efforts to address identified sex disparities are needed. Area-level HCV CVL measures may be valuable to geographically focus prevention and treatment efforts and merit further study as predictors of incidence.

PWUD engaged in MAT continue to be at risk for HCV infection. The large reservoir of PWUD chronically infected with HCV, and persistently high HCV incidence rates, reinforce the need for vigorous efforts to improve HCV care continuum outcomes and ensure access to high-quality MAT. Efforts to expand HCV treatment access and engagement are essential to promote HCV CasP and achieve HCV control among PWUD.

Available for download on Saturday, December 11, 2021

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